POS1450 3-YEAR ANALYSES OF AT-RISK ANA-POSITIVE COHORT: PROGNOSTIC VALUE OF CLINICAL AND INTERFERON BIOMARKERS TOWARDS AUTOIMMUNITY
Authors: M. Y. MD Yusof, S. U. Hassan, Z. Wigston, A. Psarras, J. Arnold, L. M. Carter, P. Emery, E. Vital
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Autoimmune connective tissue disease (AI-CTD) arise from a common "At-Risk" ANA-positive population in which clinical phenotype does not reliably predict progression. We previously showed that higher IFN-Score-B and family history were predictive of progression to meeting classification criteria at 12-months[1]. However, classification criteria may undergo revision and not capture all significant outcomes. There is limited data on longer-term outcomes since some may progress at later time-points. <h3>Objectives</h3> To describe the 3-year outcomes of At-Risk individuals; to assess discriminative ability of baseline clinical and IFN-Score-B in predicting various progression endpoints at 1 and 3 years. <h3>Methods</h3> We conducted a prospective cohort study in At-Risk individuals (ANA-positive, non-specific symptoms of ≤1 year and treatment naïve). Patients were assessed at baseline, then annually for 3 years. We used multiple RMD classification criteria, including the revised 2019 EULAR/ACR for SLE, and need for therapy, to group patients as below: 1. Absolute non-progressors (ANP) (no clinical criteria) 2. Undifferentiated CTD (U-CTD) (≥1 clinical criteria but not fulfilling RMD criteria). This group was subdivided into those requiring an immunosuppressant (IS) excluding antimalarials only and those who did not) 3. Year 1 progressors (meeting criteria for RMD by 1 year) 4. Late progressors (meeting criteria for RMD in Years 2-3) 5. Clinically significant disease (CSD) (progressors OR U-CTD on IS) Bloods were analysed for two IFN-stimulated gene expression scores previously described[2]. Discrimination of single or combined clinical and IFN-Score-B markers were assessed using ROC curve analyses. <h3>Results</h3> Of 148 patients, 132 (89%) were female, 107 (72%) were Caucasians, 48 (32%) had a family history of RMD, 56 (38%) were anti-dsDNA+ and 8 (6%) had low C3 and/or C4 level. Number of established clinical criteria at baseline were 0 (30%), 1 (64%) and 2 (6%). Outcomes were: Year 1 progressors: 21 (14%) [SLE=14; pSS=6; AS=1]; Late progressors: 12 (8%) [SLE=10; pSS=1; AS=1]; U-CTD on IS: 8 (5%); U-CTD on antimalarials only: 20 (14%); U-CTD not on therapy: 52 (35%) and ANP: 35 (24%). Thus, 41 (28%) patients were classified as CSD. Only 2/148 (1%) patients progressed after the first 2 years. For the prediction of Year 1 progressor, in addition to baseline IFN-Score-B and family history, multivariable logistic regression showed total number of any established clinical criteria was associated with increased risk, OR 6.8 (95% CI 1.8-25.4). Table 1 showed that the combined baseline markers (IFN-Score-B, family history and number of clinical criteria) had good accuracy in predicting various definitions of progression at Years 1 and 3 as per AUROC. <h3>Conclusion</h3> Just over a quarter of At-Risk individuals developed into CSD (progressors and patients who did not meet criteria but needed IS therapy) by 3-year follow-up. Combined baseline clinical and IFN biomarkers could be used to risk stratify ANA-positive referrals to rheumatology at the first visit to exclude imminent or future disease/requirement of immunosuppressant. A validation study with cost-effectiveness analysis of these markers is in progress and would help translate their use in clinical practice and inform early therapy trials in the "High Risk" individuals. <h3>References</h3> [1]Md Yusof MY et al. Ann Rheum Dis 2018 [2]El-Sherbiny Y et al. Sci Rep 2018 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Md Yuzaiful Md Yusof Consultant of: Aurinia Pharmaceuticals and UCB, Sabih Ul Hassan: None declared, Zoe Wigston: None declared, Antonios Psarras: None declared, Jack Arnold: None declared, Lucy Marie Carter Consultant of: UCB, Paul Emery Consultant of: Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche and Samsung, Grant/research support from: Abbvie, BMS, Eli Lilly, Pfizer, Novartis, Roche and Samsung, Edward Vital Speakers bureau: AstraZeneca, Novartis, Paid instructor for: AstraZeneca, Novartis, Consultant of: UCB, Pfizer, Aurinia, Lilly, Roche, Genentech, Otsuka, GSK, Capella, Grant/research support from: Sandoz, AstraZeneca.